With a rising number of patients diagnosed with breast cancer and lymphoma, Polish researchers at the Medical University of £ód¼, working in collaboration with experts from biotechnology company Mabion, have developed two innovative biotech drugs to fight these tumors. The project is part of worldwide efforts to come up with more effective ways of combating breast cancer and lymphoma.

Unlike standard chemotherapy, biotech drugs are far less harmful to the patient, the researchers say. However, most biotech drugs available internationally carry a steep price tag and many patients in Poland cannot afford them. The Polish drugs are expected to be less expensive.

One of the drugs developed by the £ód¼ researchers has been obtained as part of a project called “the development of a humanized monoclonal antibody that binds to the CD20 receptor and can be used in the treatment of lymphomas.” The other drug has been generated in a project called “the development of a humanized monoclonal antibody that binds to the HER2 receptor and can be used in the treatment of breast cancer.”

The research team, led by Prof. Tadeusz Pietrucha, who heads the Department of Medical Biotechnology at the Medical University of £ód¼, began working on the drugs in 2008. At the moment, the project is being developed and implemented in a biotechnology company and is at the clinical trial stage.

The idea to produce technologically advanced Polish drugs based on humanized monoclonal antibodies came from Maciej Wieczorek, Ph.D., CEO of the Celon Pharma company, who worked with Pietrucha’s team. As a business partner he was aware of the needs of the pharmaceutical market. He was also aware of the importance of innovative biotechnology in modern medicine.

Two grants awarded under the Technology Initiative Program played an important role in launching work on the anticancer drugs. The grants made it possible to finance the most risky part of this project—the early laboratory tests stage.

However, those early efforts were not scientific in nature in the strict sense of the word, Pietrucha says. The aim was mainly to develop a product much needed for these two groups of cancer patients.

“Back then, in early 2008, there was no other biotechnology project being carried out in Poland on such a large scale,” says Pietrucha. “The project was so ambitious, risky and difficult that six companies from the pharmaceutical and biotechnology sectors set up the Mabion company to take care of its full implementation—from obtaining a formula for the pharmaceuticals in the laboratory to putting them into production and placing them on the market.”

When a foreign body such as a bacterium or virus appears, the human body produces antibodies to destroy it. But the problem is that the patient’s body often fails to recognize cancer cells as hostile. After all, these are the patient’s own cells. Medicine already knows how to enable anti-cancer drugs to identify cancer cells. This involves the use of monoclonal antibodies capable of identifying specific breast cancer and lymphoma cells and of destroying them.

There is one condition though—they cannot be produced in a human body. This non-human body will then identify human cancer cells as foreign. However, in order to make sure that antibodies produced in an non-human body can be applied in humans, these antibodies must be “humanized”—which means made similar to antibodies produced by the human body.

The biotech drugs developed by Polish scientists are based on monoclonal antibodies, or antibodies that accurately identify their target—cancer cells. These are so-called targeted drugs that work selectively, zeroing in only on cells with specific markers characteristic of the cancer cells, without affecting healthy cells. They are more effective, up to 50 percent more effective, than standard cancer treatment methods based on surgery, radiation therapy, and chemotherapy, which damage not only cancer cells but also healthy tissue.

“A biotech drug is most often an active protein with the same composition of amino acids as the corresponding protein produced by the human body,” says Pietrucha. “We have obtained these proteins through the use of modern cloning, molecular biology and genetic engineering techniques. We introduced the gene encoding them into the line of host cells and these cells were in a way forced to produce the proteins we needed.”

In the earliest, initial phase of the project, the researchers undertook to check if the research teams working together on a laboratory scale would be capable of generating these types of antibodies with desirable therapeutic properties.

There are so many difficulties involved in producing such a protein that so far no Polish pharmaceutical company has managed to complete the process: from obtaining the protein in laboratory conditions, to developing the formula and production technology, to conducting tests on animals and carrying out all four phases of clinical trials, to carrying out the registration process, to putting the drug on the market.

Cancer cells, much as healthy human cells, contain certain characteristic markers on their surface. A drug is needed, for example a protein—a monoclonal antibody—to track down and identify this marker, identify the cancer cell cluster as hostile and subsequently destroy it.

Thanks to advances in molecular biology and cracking the genetic code, scientists know what genes are responsible for the formation of such antibodies. The problem is that most often researchers obtain antibodies of, for instance, mice, which identify these markers in human cancer cells. If these antibodies are administered in such a form, the human body will protest and will seek to destroy them: after all this will be a foreign protein. The only solution is to humanize such a protein, which means make it similar to those found in people. Therefore it is necessary to replace the mouse amino acids sequences that the protein is made up of with human amino acid sequences. In other words, some parts of the mouse protein need to be replaced with the corresponding fragments of the human protein. After such a replacement, the patient’s body can be fooled and will identify the antibody as its own. And it will then start to fight the cancer cells. “Using biotechnology methods, we can produce such antibodies on a massive scale,” says Pietrucha.

The whole procedure applies to the two projects on which the consortium of the University of £ód¼ researchers and Mabion company employees is working. It was first necessary to check if the technology for obtaining drugs on a laboratory scale could be a starting point for developing a technology for use on an industrial scale, while meeting the necessary requirements. This led to the launch of Poland’s first factory capable of producing such complex biotech drugs. The technology for producing humanized monoclonal antibodies, while taking into account the requirements of production on an industrial scale, has been developed directly at the Mabion company in £ód¼. This technology had to be in line with not only legal regulations, but also stringent requirements formulated by the European Medicine Agency (EMA), an international body clearing biotech drugs for sale on markets across the European Union.

Such technologies need to be developed essentially from scratch, the researchers say, regardless of the stage carried out in the research laboratory. A market worth hundreds of millions of zlotys could be at stake. But first it is necessary to invest millions of zlotys to launch production of these pharmaceuticals. Building a biotechnology research and industrial complex in the £ód¼ Special Economic Zone is expected to cost a further zl.35 million. The company is expected to be ready to launch mass production of the two innovative drugs in 2013.

Currently work is at an advanced stage on implementing both drugs, now entering a phase of accelerated clinical trials. The final success of the project will depend on the EMA. If the agency approves the drug, this will mean not only clearing the drug itself, but also the method for producing it in terms of whether it is safe for patients and meets the necessary standards. This process may take around two years.Danuta K. Gruszczyńska